Cardiac apoptosis induced under high glucose condition involves activation of IGF2R signaling in H9c2 cardiomyoblasts and streptozotocin-induced diabetic rat hearts

Chih Chung Feng, Sudhir Pandey, Ching Yuang Lin, Chia Yao Shen, Ruey Lin Chang, Tung Ti Chang, Ray Jade Chen, Vijaya Padma Viswanadha, Yueh Min Lin, Chih Yang Huang

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

The insulin-like growth factor type 2 receptor (IGF2R) overexpression has been implicated in heart disease progression. Unregulated IGF2R signaling triggers cardiac hypertrophy, apoptosis, and cardiomyopathies. The present study investigated the role of IGF2R in cardiomyocyte apoptosis under high glucose (HG) levels and in streptozotocin (STZ) induced diabetic rat hearts. We found that IGF2 and IGF2R protein expression were highly upregulated under high glucose condition in H9c2 cells as well as in STZ induced diabetic rat hearts. Using immunoblotting and TUNEL assay, we found that elevated glucose condition induced IGF2R expression leads to activation of Gαq mediated calcineurin-dependent signaling pathway, which further leads to downstream activation and expression of cardiac hypertrophy related proteins, ANP and BNP. Further, we found that glucose-induced IGF2R expression downregulated survival protein p-Akt, p-Bad (Ser 155) and enhanced the expression of apoptosis-inducing proteins cytochrome c and cleaved Caspase-3. Our results suggested that hyperglycemic condition leads to cellular cardiomyocyte apoptosis both in vitro and in vivo models, via abnormally increased activation of the IGF2R signaling pathway.

Original languageEnglish
Pages (from-to)880-885
Number of pages6
JournalBiomedicine and Pharmacotherapy
Volume97
DOIs
Publication statusPublished - Jan 1 2018

Keywords

  • Apoptosis
  • Diabetic hyperglycemic
  • High glucose (HG)
  • IGF2R

ASJC Scopus subject areas

  • Pharmacology

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